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• Credits

  • Section Writer: Dr. Om J Lakhani
  • Section Editor: Dr. Om J Lakhani

• For corresponding notes for patients in simple language, please click the link below

  • Basics about Steroids

• Q. What are glucocorticoids?

  • They are a class of corticosteroids, i.e., Steroid hormones that produce the Adrenal cortex
  • They bind to glucocorticoid receptors

• Q. What is the use of glucocorticoids in endocrinology?

  • Diagnosis of Cushing's syndrome
  • Treatment of adrenal insufficiency
  • Treatment of Congenital adrenal hyperplasia (CAH)
  • Treatment of glucocorticoid remediable hypertension
  • Treatment of active Graves ophthalmopathy
  • Treatment of thyroid storm

• Pharmacokinetics

• Q. How do endogenous Glucocorticoids circulate in the blood?

  • Majority of the glucocorticoids are in the bound state bound to Cortisol binding globulin (CBG) or albumin
  • Free glucocorticoids may also be bound to RBCs

• Q. How do synthetic glucocorticoids circulate in blood?

  • They do not bind with CBG
  • They are loosely bound to albumin

• Q. Which synthetic glucocorticoid does bind to CBG?

  • Prednisolone

• Q. What is the half-life of endogenous Cortisol?

  • 80 min

• Q. What is the role of 11 beta HSD1? Where is it located?

  • It converts cortisone to Cortisol
  • It is found in most of the target tissues for glucocorticoid action

• Q. What about 11 beta HSD2?

  • It inactivates Cortisol
  • It converts Cortisol to cortisone
  • It is found in mineralocorticoid action tissue like
    • Kidney
    • Placenta
    • Colon
    • Salivary glands

• Q. Which are the fluorinated glucocorticoids?

  • Dexamethasone
  • Fludrocortisone
  • Triamcinolone

• Q. Which are the other modifications to glucocorticoids?

  • Methylated- Methylprednisolone
  • Methyoxazoline addition – deflazacort

• Q. What is the effect of fluorination/methylation on Pharmacokinetics ?

  • Reduces inactivation by 11 beta HSD2

• Q. What about prednisone ?

  • It is more effectively metabolized by 11 beta HSD2 than Cortisol
  • Hence it has a more negligible mineralocorticoid effect

• Q. Which drugs reduce the efficacy of Glucocorticoids by causing CYP34A enzyme induction?

  • Rifampicin
  • Anticonvulsants
  • Efavarinez

• Q. Which drugs inhibit CYP3A4 enzymes, which cause toxicity due to glucocorticoids?

  • Cyclosporine and tacrolimus
  • Ritonavir
  • Isoniazid
  • Antifungals- ketoconazole, itraconazole
  • Estrogen

• Q. Which glucocorticoids are not affected by the CYP3A4 mechanism?

  • Prednisolone

• Q. What are the various bioassays for glucocorticoids?

  • 1. lowering eosinophil count in humans
  • 2. stimulation of hepatic glycogen deposition
  • 3. inhibit inflammation after subcutaneous oil injection in rodents

• Q. What is the bioassay for Mineralocorticoid activity?

  • Ability to inhibit sodium excretion in adrenalectomized rats

• Q. Give the equivalent potencies of various glucocorticoids?

  • Prednisolone 5 mg is equal to
    • Hydrocortisone 20 mg
    • Methylprednisolone 4 mg
    • Dexamethasone 0.75 mg

• Q. What time does the oral preparation of glucocorticoids take for absorption?

  • 30 min
  • With good bioavailability

• **THERAPEUTIC USE OF GLUCOCORTICOIDS **

• Q. What are the principles to follow when using glucocorticoids therapeutically?

  • A clear benefit of the use should be identified
  • glucocorticoids must be used only when other therapies are not an option or have failed
  • A specific therapeutic objective, duration or treatment, and objective criteria for response must be identified before starting treatment
  • Consider terminating if the therapeutic objective and response is not achieved
  • Steroid sparing regimens must be constantly considered in a long run
  • Non-systemic steroids are always preferred
  • Whenever given, care must be taken to provide glucocorticoid in the lowest possible dose in the most physiological way in which it is possible

• Q. What is the mechanism of anti-inflammatory action of glucocorticoids?

  • They act by trans-repression of Nuclear factor Kappa B (NF- kB)
  • NF-kB is a mediator of inflammatory action of TNF alpha

• Q. Do inhaled, and topical steroids also cause hypothalamic–pituitary–adrenal (HPA) axis suppression ?

  • Yes

• Q. Which inhaled steroid is notorious for HPA axis suppression?

  • Fluticasone

• Q. Does the site of local application affect HPA axis suppression ?

  • Yes
  • In sequence of likelihood of causing suppression
    • intertriginous areas > forehead > scalp > face > forearm

• Q. Which vehicles used to increase systemic absorption ?

  • Urea
  • Salicylate
  • Dimethylsulphoxide

• Q. Which other factors affect systemic absorption ?

  • presence of occlusive dressing
  • breach of the skin or tissue due to inflammation
  • Age of the patient- more absorption at extremes of age

• Q. What are the lowest doses of glucocorticoids that can affect linear growth in children ?

  • Doses as low as
    • 0.075 mg/kg of prednisolone
    • 0.3 mg/kg of hydrocortisone

• Q. Is alternate-day therapy successful in preventing HPA axis suppression ?

  • No

• Q. Which patients are more likely to have HPA axis suppression with glucocorticoids ?

  • Prednisolone > 20 mg for >3 weeks
  • Prednisolone >5mg at night-time > 2 weeks
  • Patient having clinical features of iatrogenic Cushing's

• Q. Which clinical features are more common in iatrogenic Cushing compared to endogenous Cushing's?

  • Benign Raised ICT
  • Osteonecrosis of femoral head
  • Posterior subcapsular cataract
  • Glaucoma
  • Panniculitis
  • Pancreatitis
  • Spinal epidural lipomatosis

#Updates Sunday, 12 September 2021

• Q. What is Glucocorticoid-Induced Leucine Zipper (GILZ)?

  • Glucocorticoids have potent anti-inflammatory actions.
  • However, they have significant long-term side effects.
  • Researchers have now identified a new gene called glucocorticoid-induced leucine zipper (GILZ or tsc22d3) induced by Glucocorticoids.
  • Activation of this gene leads to activation of NF-κB and MAPK pathways that are the core process by which glucocorticoids induce their anti-inflammatory action.
  • Identification of this gene could pave the way to the development of new drugs that could activate this gene without causing long term side effects. ^[1]

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